The agaricus bisporus mushroom extract modulates liver fibrosis progression, oxidative stress and inflammation in vitro and in Ldlr-KO mice models

2021 ◽  
Vol 46 ◽  
pp. S677-S678
Author(s):  
A. Luque-Sierra ◽  
P. Gallego-Yerga ◽  
L. Grande ◽  
J. Bautista ◽  
F. Martín ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Agaricus Bisporus ◽  
Mushroom Extract ◽  
Fibrosis Progression

scholarly journals White Button Mushroom Extracts Modulate Hepatic Fibrosis Progression, Inflammation, and Oxidative Stress In Vitro and in LDLR-/- Mice

Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1788
Author(s):  
Paloma Gallego ◽  
Amparo Luque-Sierra ◽  
Gonzalo Falcon ◽  
Pilar Carbonero ◽  
Lourdes Grande ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Stellate Cell ◽  
Water Soluble ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Fibrosis Progression ◽  
And Oxidative Stress

Liver fibrosis can be caused by non-alcoholic steatohepatitis (NASH), among other conditions. We performed a study to analyze the effects of a nontoxic, water-soluble extract of the edible mushroom Agaricus bisporus (AB) as a potential inhibitor of fibrosis progression in vitro using human hepatic stellate cell (LX2) cultures and in vivo in LDLR-/- mice. Treatment of LX2 cells with the AB extract reduced the levels of fibrotic and oxidative-related markers and increased the levels of GATA4 expression. In LDLR-/- mice with high-fat diet (HFD)-induced liver fibrosis and inflammation, the progression of fibrosis, oxidative stress, inflammation, and apoptosis were prevented by AB extract treatment. Moreover, in the mouse model, AB extract could exert an antiatherogenic effect. These data suggest that AB mushroom extract seems to exert protective effects by alleviating inflammation and oxidative stress during the progression of liver fibrosis, possibly due to a decrease in Toll-like receptor 4 (TLR4) expression and a reduction in Nod-like receptor protein 3 (NLRP3) inflammasome activation. In addition, we observed a potential atheroprotective effect in our mouse model.

scholarly journals Fighting Liver Fibrosis with Naturally Occurring Antioxidants

Planta Medica ◽  
2018 ◽  
Vol 84 (18) ◽  
pp. 1318-1333 ◽  
Author(s):  
Ligen Lin ◽  
Fayang Zhou ◽  
Shengnan Shen ◽  
Tian Zhang
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Normal Liver ◽  
Natural Antioxidants ◽  
In Vivo Studies ◽  
Lead Compounds ◽  
Naturally Occurring ◽  
Wound Healing Response

AbstractLiver fibrosis is a wound-healing response characterized by the accumulation of extracellular matrix following various liver injuries, which results in the deformation of the normal liver architecture and the development of liver cirrhosis and even hepatocellular carcinoma. Numerous in vitro and in vivo studies indicated that oxidative stress mediates the initiation and progression of liver fibrosis. Overaccumulation of reactive oxygen species disrupts macromolecules, induces necrosis and apoptosis of hepatocytes, stimulates the production of pro-fibrogenic mediators, and directly activates hepatic stellate cells, thereby resulting in liver damage and initiating liver fibrosis. Ameliorating oxidative stress is a potential therapeutic strategy for the treatment of liver fibrosis. Natural antioxidants have attracted increasing attention in treating liver fibrosis due to their safety and efficacy. In this review, the pathogenesis of liver fibrosis and the role of oxidative stress in liver fibrosis were discussed. Naturally occurring antioxidants that can treat and prevent liver fibrosis were summarized. Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of oxidative stress in liver fibrosis to representative antioxidants for treating liver fibrosis. Naturally occurring antioxidants show a potential for further investigations as lead compounds in fighting liver fibrosis.

Combination treatment of angiotensin II type I receptor blocker and new oral iron chelator attenuates progression of nonalcoholic steatohepatitis in rats

2011 ◽  
Vol 300 (6) ◽  
pp. G1094-G1104 ◽  
Author(s):  
Kosuke Kaji ◽  
Hitoshi Yoshiji ◽  
Mitsuteru Kitade ◽  
Yasuhide Ikenaka ◽  
Ryuichi Noguchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
Angiotensin Ii ◽  
Liver Fibrosis ◽  
Combination Treatment ◽  
Iron Chelator ◽  
Receptor Blocker ◽  
Type I ◽  
Oral Iron Chelator

Angiotensin II type I receptor blocker and iron chelator reportedly exert suppressive effects on nonalcoholic steatohepatitis (NASH) progression, including liver fibrosis and hepatocarcinogenesis. The aim of this study was to elucidate the combined effect of losartan (LOS), an angiotensin II type I receptor blocker, and deferasirox (DSX), a newly developed oral iron chelator, on the progression of NASH in rats. To induce NASH, F344 rats were fed a choline-deficient l-amino acid-defined diet for 12 wk, and the effects of LOS and DSX at clinically comparable low doses were elucidated in conjunction with oxidative stress, neovascularization, and hepatic stellate cells (HSC) activation, all known to play important roles in the progression of NASH. Treatment with both LOS and DSX suppressed choline-deficient l-amino acid-defined diet-induced liver fibrosis development and hepatocarcinogenesis. This combination treatment exerted a stronger inhibitory effect compared with treatment with a single agent. These inhibitory effects occurred almost concurrently with the suppression of oxidative stress, neovascularization, and HSC activation. Our in vitro study demonstrated that LOS and DSX inhibited angiotensin II-induced proliferation, transforming growth factor-β1 expression of activated HSC, and in vitro angiogenesis. These results indicated that dual inhibition by combined treatment of LOS and DSX attenuated the progression of NASH. Since both agents are widely used in clinical practice, this combination therapy may represent a potential new strategy against NASH in the near future.

scholarly journals Chitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis

2021 ◽  
Vol 118 (17) ◽  
pp. e2019633118
Author(s):  
Norihisa Nishimura ◽  
Davide De Battista ◽  
David R. McGivern ◽  
Ronald E. Engle ◽  
Ashley Tice ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Fibrosis ◽  
Liver Tissue ◽  
Messenger Rna ◽  
Normal Liver ◽  
In Vitro Models ◽  
Hepatitis D ◽  
Fibrosis Progression ◽  
Increased Risk

Older age at the time of infection with hepatitis viruses is associated with an increased risk of liver fibrosis progression. We hypothesized that the pace of fibrosis progression may reflect changes in gene expression within the aging liver. We compared gene expression in liver specimens from 54 adult donors without evidence of fibrosis, including 36 over 40 y old and 18 between 18 and 40 y old. Chitinase 3-like 1 (CHI3L1), which encodes chitinase-like protein YKL-40/CHI3L1, was identified as the gene with the greatest age-dependent increase in expression in liver tissue. We investigated the cellular source of CHI3L1 in the liver and its function using liver tissue specimens and in vitro models. CHI3L1 expression was significantly higher in livers of patients with cirrhosis of diverse etiologies compared with controls represented by patients who underwent liver resection for hemangioma. The highest intrahepatic CHI3L1 expression was observed in cirrhosis due to hepatitis D virus, followed by hepatitis C virus, hepatitis B virus, and alcohol-induced cirrhosis. In situ hybridization of CHI3L1 messenger RNA (mRNA) identified hepatocytes as the major producers of CHI3L1 in normal liver and in cirrhotic tissue, wherein hepatocytes adjacent to fibrous septa showed higher CHI3L1 expression than did those in more distal areas. In vitro studies showed that recombinant CHI3L1 promotes proliferation and activation of primary human hepatic stellate cells (HSCs), the major drivers of liver fibrosis. These findings collectively demonstrate that CHI3L1 promotes liver fibrogenesis through a direct effect on HSCs and support a role for CHI3L1 in the increased susceptibility of aging livers to fibrosis progression.

Chlorogenic acid protects against liver fibrosis in vivo and in vitro through inhibition of oxidative stress

2016 ◽  
Vol 35 (6) ◽  
pp. 1366-1373 ◽  
Author(s):  
Haitao Shi ◽  
Ameng Shi ◽  
Lei Dong ◽  
Xiaolan Lu ◽  
Yan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Chlorogenic Acid

Multi-omics analysis of aspirin treatment response in mice provide molecular insights and targets linked to liver fibrosis regression

2020 ◽  
Author(s):  
Adil Bhat ◽  
Sudrishti Chaudhary ◽  
Gaurav Yadav ◽  
Anupama prasar ◽  
Chhagan Bihari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Tryptophan Metabolism ◽  
Metabolome Analysis ◽  
Beneficial Effects ◽  
Arginase 1 ◽  
Cross Correlation Analysis ◽  
Fibrosis Regression

AbstractBackground & AimsAspirin has potent anti-platelet activities and possibly helps regression of fibrosis. We investigated antifibrotic mechanisms of aspirin in the murine CCl4 model and in patients with hepatic fibrosis.MethodsMultiomics analysis identified networks and molecular targets regulated by aspirin which were validated in murine model and in patients with liver fibrosis.ResultsBiochemical/histopathological changes and hepatic fibrosis were greater in CCl4-treated mice compared to CCl4-aspirin (CCl4+ASA) or control mice (p<0.05). In CCl4+ASA mice, integrated proteome-metabolome analysis showed an increase in autophagy, drug metabolism, glutathione and energy metabolism (p<0.05) and decrease in inflammatory pathways, arachidonic acid and butanoate metabolism (p<0.05). Global cross-correlation analysis linked fibrosis markers with protein-metabolite pathways (r2>0.5, p<0.05). Liver proteome enrichment for immune clusters using blood transcription module correlated with histidine and tryptophan metabolism (r2>0.5, p<0.05). Aspirin decreased Ryanodine-receptor-2 (RYR2;oxidative-stress), Arginase-1 (ARG-1;urea cycle), Arachidonate-5-lipoxygenase (ALOX5;leukotriene metabolism), and Kynurenine-3-monooxygenase (KMO;tryptophan metabolism; p<0.05) which correlated with reduction in α-SMA, PDGFR-β and degree of hepatic fibrosis (r2>0.75; p<0.05) in animal and human studies, and, in-vitro analysis. Aspirin modulated intracellular-calcium and oxidative-stress levels by reducing RYR2 expression in activated LX-2 cells. It modulated the liver microbiome and its functions which also correlated with ARG1, ALOX5, RYR2 expression (r2>0.5, p<0.05). Metaproteome analysis showed significant microbiome similarity at phylum level in murine liver tissues and fecal samples. Aspirin increased the abundance of Firmicutes (Ruminococcaceae, Lachnospiraceae, and Clostridiaceae) and their functionality, as assessed by glycerol-3-phosphate dehydrogenase (NAD(P)(+) and dTMP-kinase activity (p<0.05).ConclusionsAspirin demonstrates broad beneficial effects following oxidative injury, inflammation, and hepatic fibrosis. Aspirin induces distinctive hepatic proteome/metabolome and intrahepatic microbiome changes which are indicative of fibrosis regression and could be further explored as therapeutic targets.

scholarly journals Ruxolitinib Suppresses Liver Fibrosis Progression and Accelerates Fibrosis Reversal via Selectively Targeting Janus Kinase 1/2

2021 ◽  
Author(s):  
Zhenghui Song ◽  
Xinhui Liu ◽  
Wan Zhang ◽  
Yue Luo ◽  
Hua Xiao ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Tissue ◽  
Cell Damage ◽  
Underlying Mechanism ◽  
Janus Kinase ◽  
Human Liver Tissue ◽  
Downstream Signaling ◽  
Fibrosis Progression ◽  
And Migration

Abstract BackgroundJAK1 and JAK2 have been implicated in fibrosis and cancer as a fibroblast-related marker; however, their role in liver fibrosis has not been elucidated. Here, we aim to determine the effect and underlying mechanism of JAK1/2 inhibition on liver fibrosis and hepatic stellate cells (HSCs) and further explore the therapeutic efficacy of Ruxolitinib, a JAK1/2 selective inhibitor, on preventing and reversing liver fibrosis in mice. MethodsImmunohistochemistry staining of JAK1 and JAK2 were performed on liver tissue in mice with hepatic fibrosis and human liver tissue microarray of liver cirrhosis and liver cancer. LX-2 cells treated with specific siRNA of JAK1 and JAK2 were used to analysis activation, proliferation and migration of HSCs regulated by JAK1/2. The effects of Ruxolitinib (JAK1/2 inhibitor) on liver fibrosis were studied in LX-2 cells and two progressive and reversible fibrosis animal models (carbon tetrachloride (CCl4), Thioacetamide (TAA)). ResultsWe found that JAK1/2 expression was positively correlated with the progression of HCC in humans and the levels of liver fibrosis in mice. Silencing of JAK1/2 down-regulated their downstream signaling and inhibited proliferation, migration, and activation of HSCs in vitro, while Ruxolitinib had similar effects on HSCs. Importantly, Ruxolitinib significantly attenuated fibrosis progression, improved cell damage, and accelerated fibrosis reversal in the liver of mice treated with CCl 4 or TAA. ConclusionsJAK1/2 regulates the function of HSCs and plays an essential role in liver fibrosis and HCC development. Its inhibitor, Ruxolitinib, may be an effective drug for preventing and treating liver fibrosis.

scholarly journals Astaxanthin Prevents Diet-Induced NASH Progression by Shaping Intrahepatic Immunity

2021 ◽  
Vol 22 (20) ◽  
pp. 11037
Author(s):  
Ming Yang ◽  
Eric T. Kimchi ◽  
Kevin F. Staveley-O’Carroll ◽  
Guangfu Li
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Stellate Cell ◽  
In Vitro Studies ◽  
Alcoholic Fatty Liver ◽  
Duct Ligation

Dietary change leads to a precipitous increase in non-alcoholic fatty liver disease (NAFLD) from simple steatosis to the advanced form of non-alcoholic steatohepatitis (NASH), affecting approximately 25% of the global population. Although significant efforts greatly advance progress in clarifying the pathogenesis of NAFLD and identifying therapeutic targets, no therapeutic agent has been approved. Astaxanthin (ASTN), a natural antioxidant product, exerts an anti-inflammation and anti-fibrotic effect in mice induced with carbon tetrachloride (CCl4) and bile duct ligation (BDL); thus, we proposed to further investigate the potential effect of ASTN on a diet-induced mouse NASH and liver fibrosis, as well as the underlying cellular and molecular mechanisms. By treating pre-development of NASH in mice induced with a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD), we have demonstrated that oral administration ASTN preventively ameliorated NASH development and liver fibrosis by modulating the hepatic immune response, liver inflammation, and oxidative stress. Specifically, ASTN treatment led to the reduction in liver infiltration of monocyte-derived macrophages, hepatic stellate cell (HSC) activation, oxidative stress response, and hepatocyte death, accompanied by the decreased hepatic gene expression of proinflammatory cytokines such as TNF-α, TGF-β1, and IL-1β. In vitro studies also demonstrated that ASTN significantly inhibited the expression of proinflammatory cytokines and chemokine CCL2 in macrophages in response to lipopolysaccharide (LPS) stimulation. Overall, in vivo and in vitro studies suggest that ASTN functions as a promising therapeutic agent to suppress NASH and liver fibrosis via modulating intrahepatic immunity.

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